The importance of local Ca2+ control beneathe the T-tubule membrane in cardiomyocytes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26702014
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Kawasaki Medical School
• Principal Investigator: Ujihara Yoshihiro 川崎医科大学, 医学部, 助教 (80610021)
• Research Collaborator: MOHRI Satoshi 川崎医科大学, 医学部, 教授 (00294413) ; HASHIMOTO Ken 川崎医科大学, 医学部, 講師 (80341080) ; HANASHIMA Akira 川崎医科大学, 医学部, 助教 (70572981) ; KATANOSAKA Yuki 岡山大学, 大学院医歯(薬)学総合研究科, 助教 (60432639) ; HONDA Takeshi 川崎医科大学, 医学部, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: バイオメカニクス / メカノバイオロジー / メカノフィジオロジー / リモデリング / カルシウム / ホメオスタシス / T管膜 / 心不全

Outline of Final Research Achievements

Transverse tubules (T-tubules) are invaginations of the sarcolemma and critical for cardiomyocyte contraction. Therefore, T-tubule disorganization is linked to decreased contractility in heart failure. However, the molecular details have remained unclear. Na+/Ca2+ exchanger (NCX1) is essential Ca2+ regulator of myocyte Ca2+ homeostasis and preferentially localized to T-tubule membrane. We found that NCX1 activity was depressed before T-tubule disorganization during the progression of heart failure induced by pressure overload. In addition, the recovery of depressed NCX1 activity by inducing NCX1 expression prevented T-tubule disorganization and heart failure progression. These results suggest that local Ca2+ control beneath the T-tubule membrane is crucial for the maintenance of myocyte structure and function, in which NCX1 has a pivotal role.

Free Research Field

医用生体工学